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The effects of acute fluoxetine administration on temporal discounting in youth with ADHD

Carlisi, C. O., Chantiluke, K., Norman, L., Christakou, A., Barrett, N., Giampietro, V., Brammer, M., Simmons, A. and Rubia, K. (2016) The effects of acute fluoxetine administration on temporal discounting in youth with ADHD. Psychological Medicine, 46 (6). pp. 1197-1209. ISSN 0033-2917

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To link to this item DOI: 10.1017/S0033291715002731

Abstract/Summary

Background Serotonin is under-researched in attention deficit hyperactivity disorder (ADHD), despite accumulating evidence for its involvement in impulsiveness and the disorder. Serotonin further modulates temporal discounting (TD), which is typically abnormal in ADHD relative to healthy subjects, underpinned by reduced fronto-striato-limbic activation. This study tested whether a single acute dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine up-regulates and normalizes reduced fronto-striato-limbic neurofunctional activation in ADHD during TD. Method Twelve boys with ADHD were scanned twice in a placebo-controlled randomized design under either fluoxetine (between 8 and 15 mg, titrated to weight) or placebo while performing an individually adjusted functional magnetic resonance imaging TD task. Twenty healthy controls were scanned once. Brain activation was compared in patients under either drug condition and compared to controls to test for normalization effects. Results Repeated-measures whole-brain analysis in patients revealed significant up-regulation with fluoxetine in a large cluster comprising right inferior frontal cortex, insula, premotor cortex and basal ganglia, which further correlated trend-wise with TD performance, which was impaired relative to controls under placebo, but normalized under fluoxetine. Fluoxetine further down-regulated default mode areas of posterior cingulate and precuneus. Comparisons between controls and patients under either drug condition revealed normalization with fluoxetine in right premotor-insular-parietal activation, which was reduced in patients under placebo. Conclusions The findings show that a serotonin agonist up-regulates activation in typical ADHD dysfunctional areas in right inferior frontal cortex, insula and striatum as well as down-regulating default mode network regions in the context of impulsivity and TD.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Centre for Integrative Neuroscience and Neurodynamics (CINN)
Faculty of Life Sciences > School of Psychology and Clinical Language Sciences > Department of Psychology
Faculty of Life Sciences > School of Psychology and Clinical Language Sciences > Development
Faculty of Life Sciences > School of Psychology and Clinical Language Sciences > Neuroscience
Faculty of Life Sciences > School of Psychology and Clinical Language Sciences > Psychopathology and Affective Neuroscience
ID Code:53281
Publisher:Cambridge University Press

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